Project Summary/Abstract: During the past two decades, functional Magnetic Resonance Imaging (fMRI) has become ubiquitous in studies of the human brain function. Similarly, Transcranial Magnetic Stimulation (TMS) has established its role as one of the most widely used neuromodulation techniques. Both of these methods have gained popularity due to their safe and noninvasive nature in addition to their wide availability. TMS has been applied alone and in conjunction with neuroimaging methods such as fMRI to dissect the roles of specific brain regions in a variety of motor, perceptive, and cognitive processes. However, due to the limitations of currently existing TMS and imaging technologies, these approaches do not allow probing the dynamics of the distributed neuronal networks on their naturally occurring spatiotemporal scales. Present technology of simultaneous TMS and fMRI is mainly limited to single-channel stimulation, which does not allow shifting the focus of the stimulation on neuronally relevant millisecond timescales. Robotic positioning of a conventional TMS coil in the MRI environment will not enable fast stimulation of nearby targets and becomes infeasible for multi-coil setups. Here we propose a new type of integrated multichannel TMS neuromodulation and MRI parallel imaging receive coil array that allows multiple sites to be stimulated simultaneously or in rapid succession, while simultaneously recording activity from the whole brain with high spatiotemporal resolution. Our approach incorporates several innovations, which have been directly motivated by the BRAIN Initiative's goal to improve the spatiotemporal resolution of noninvasive neuromodulation. The TMS will be delivered using a new type of 16x3 multi-coil array consisting of 16 units with 3 orthogonal coils for maximal spatial control of the electric field (E-field) shaping. The current amplitudes and waveforms to stimulate a given target can be determined via an optimization algorithm, and the focus can be rapidly shifted under electronic control. The electronic control is achieved by combining the E-fields of the 16x3 TMS channels driven by 48 independent stimulators with adjustable pulse width. The rapid concurrent fMRI acquisition is accomplished by a dedicated 32-channel full- head radiofrequency (RF) receive coil helmet and subsequent parallel imaging reconstruction. With such TMS/RF coil system, a stimulation/recording sequence where the TMS activation focus is dynamically shifted can be programmed and automatically executed while simultaneously recording the brain activity with high spatiotemporal resolution. Furthermore, using on-line feedback, the stimulation/recording sequence can be made to adapt to the observed brain activity in a closed-loop fashion, for instance, to obtain a maximal response at a clinically relevant target location. This kind of integrated neuromodulation and imaging device would be transformative for clinical non-invasive brain stimulation applications including TMS treatment of depression as well as for cognitive neuroscience applications. We will test the performance of the system first in phantoms and subsequently in human subject.